Minimally invasive treatments are essential for patients with liver tumors that do not respond to chemotherapy and for patients with inoperable liver cancers. Radiofrequency (RF) and microwave (MW) ablation techniques are interstitial, focal therapies that are being used with increasing frequency for these cases. Image guidance for placement of RF or MW probes and for initial assessments of treated volumes is essential for the success of these procedures. We and others have demonstrated that ultrasound based strain and modulus imaging are promising for accurately depicting the treated volumes in ablation procedures. Initial assessments for superficial structures demonstrate high image contrast of ablated regions. Our research will develop and evaluate a novel strain imaging method termed "electrode displacement elastography," or EDE, to monitor minimally invasive ablative treatments and delineate the zone of necrosis regardless of the depth of treatment. We will initially test the effectiveness of EDE using echo data acquired with conventional curvilinear and phased arrays. This will be done by imaging custom tissue-mimicking phantoms with Young's Modulus values equivalent to that of liver tissue to determine reliability of mapping out ablated and partially ablated regions for various EDE acquisition parameters. Finite element analysis (FEA) to model deformations induced by RF/microwave displacements will be performed to better understand these experimental results. We then will evaluate 2D EDE on human patients, acquiring data at typical imaging depths and for various liver states, i.e. cirrhotic liver for hepatocellular carcinoma (HCC) and softer livers with stiffer tumors for metastases. Comparisons between EDE strain and follow-up X-ray CT images will provide crucial information on the effectiveness of EDE strain images to delineate the zone of necrosis. We will then develop and test bi-plane and three-dimensional (3D) volumetric EDE strain and modulus imaging using a 2D matrix phased array transducer. Accuracy of ablation boundary delineation for different echo data acquisition conditions will be determined using tissue-mimicking phantoms. In-vivo studies will then be conducted to test bi-plane and 3D EDE for strain and modulus imaging both on a wood-chuck HCC model and a rabbit VX2 metastases model to evaluate depiction and delineation of cancers before and after ablation therapy. Comparisons of the strain and modulus images with histopathology using light microscopy of ablated tissue will be performed. Finally, a pilot study will be performed using percutaneous bi-plane and 3D EDE on human patients. Successful completion of these studies will pave the way for clinical trials using EDE for monitoring minimally invasive ablative therapies. Incidence of HCC has doubled in the last decade, with a mortality rate of 3-6 months without treatment. The clinical significance of accurate ultrasound-based guidance for ablation treatments will be high, both in terms of reducing patient morbidity and of lowering treatment costs.

Public Health Relevance

We propose to develop a noninvasive and nonionizing approaches using ultrasound based strain and modulus imaging to monitor minimally invasive ablative therapies such as radiofrequency and microwave ablation for treating primary liver tumors and metastases. Treatment monitoring is essential since local recurrence rates after RF ablative therapy are as high as 34-55%, due in part to the inability to accurately visualize and delineate the zone of necrosis in the region treated.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA112192-07
Application #
8691741
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Tandon, Pushpa
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Physics
Type
Schools of Medicine
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
Omari, Eenas A; Varghese, Tomy (2014) Signal to noise ratio comparisons for ultrasound attenuation slope estimation algorithms. Med Phys 41:032902
Ma, Chi; Varghese, Tomy (2014) Analysis of 2-d ultrasound cardiac strain imaging using joint probability density functions. Ultrasound Med Biol 40:1118-32
Rubert, Nicholas; Varghese, Tomy (2014) Mean scatterer spacing estimation in normal and thermally coagulated ex vivo bovine liver. Ultrason Imaging 36:79-97
Rubert, Nicholas; Varghese, Tomy (2014) Scatterer number density considerations in reference phantom-based attenuation estimation. Ultrasound Med Biol 40:1680-96
Ingle, Atul; Varghese, Tomy (2014) C-plane Reconstructions from Sheaf Acquisition for Ultrasound Electrode Vibration Elastography. Proc IEEE Ultrason Symp 2014:1826-1829
Wang, Xiao; Jackson, Daren C; Varghese, Tomy et al. (2014) Correlation of cognitive function with ultrasound strain indices in carotid plaque. Ultrasound Med Biol 40:78-89
Ingle, Atul; Varghese, Tomy (2014) Three-dimensional sheaf of ultrasound planes reconstruction (SOUPR) of ablated volumes. IEEE Trans Med Imaging 33:1677-88
Cao, Rui; Huang, Zhihong; Varghese, Tomy et al. (2013) Tissue mimicking materials for the detection of prostate cancer using shear wave elastography: a validation study. Med Phys 40:022903
Ma, Chi; Varghese, Tomy (2013) Comparison of cardiac displacement and strain imaging using ultrasound radiofrequency and envelope signals. Ultrasonics 53:782-92
Xu, Haiyan; Varghese, Tomy (2013) Normal and shear strain imaging using 2D deformation tracking on beam steered linear array datasets. Med Phys 40:012902

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